Targeted Protein Degradation by Proteasomal, Lysosomal & Autophagy Pathways 2022: an industry landscape analysis of stakeholders, technologies, pipeline, partnering and financing

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Publisher: La Merie Publishing
Pages: 553
Format: PDF
Product Line: Full Report
Product Code: LMFR0036
Release Date: March of 2022
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Targeted Protein Degradation by Proteasomal, Lysosomal & Autophagy Pathways 2022:
an industry landscape analysis of stakeholders, technologies, pipeline, partnering and financing

This report describes and analyzes the field of Targeted Protein Degradation (TPD) from an industry perspective as of March 2022.

The report provides essential information about and analysis of

  • Pure-play TPD technology companies (molecular glues, heterobifunctional degraders, lysosomal and autophagic pathway degraders);
  • Diversified technology companies with a TPD platform;
  • Major pharma companies with a stake in TPD (in-house, partnering, licensing, acquisition);
  • Proteasomal protein degrader technologies (heterobifunctional, molecular glue, monovalent degrader);
  • Rational approaches for monofunctional molecular glue discovery at industry scale;
  • Lysosomal and autophagy pathway degrader technologies (LYTACs, AUTOTACs, ATTECs etc);
  • Clinical and preclinical experience with molecular glues and PROTACs;
  • Profiles of TPD Drug Candidates;
  • TPD Pipeline Analysis;
  • Preferred Targets of TPDs;
  • Preferred E3 ligases and their binders;
  • Technologies for discovery of binders to proteins-of-interest and E3 ligases;
  • Venture capital financing of TPD technology companies;
  • Financing by IPO and follow-on public offerings;
  • Revenues from TPD discovery and licensing deals.

Targeted protein degradation is a strongly and rapidly emerging new therapeutic modality based on the promise to overcome limitations of traditional small molecule drug modalities, such as limited access to difficult-to-drug targets and development of drug resistance. TPD technology is being adopted by most major pharmaceutical companies as it is regarded as a key technology platform. Pure-play TPD technology companies make progress by advancing their drug candidates into clinical studies. Many biotech companies are diversifying their platforms by adding TPD technology.

Investors welcome companies with TPD technologies as evidenced by the continuous flow of money to foster development of TPD technology and TPD drug candidates. Since April of 2020, five pure-play TPD technology companies went public and successfully raised a total of US$ 2.14 bln. The average market capitalization of five NASDAQ listed TPD technology companies was US$ 1.5 bln as of March 4, 2022. Series A-E financing rounds of 23 pure-play TPD technology companies brought in a total of US$ 1,778 mln of venture capital and equity investment. Partnering revenues are another important source of funding. As the TPD pipeline is maturing with favorable clinical outcomes, a recent licensing deal for a clinical phase II estrogen receptor PROTAC justified up-front payment and equity investment of US$ 1 bln.

This report describes and analyzes the industry landscape of targeted protein degradation by proteasomal-, lysosomal- and autophagy-targeted technologies. The report is based on information retrieved from 69 technology companies, 23 pharmaceutical companies and three academic institutions with publicly known industry ties.

The report includes Tables which summarize specific information to allow comprehensive comparisons. Illustrations are used to explain the mechanism of action of the various TPD technologies, pharmacologic effects and molecular structures.

Whenever possible, the profiles of TPD technology companies address the following aspects:

  • General overview (founders, foundation year, technology source, location, number of employees), non-TPD technologies if applicable;
  • Financial situation and funding history;
  • Technology overview;
  • Partnering;
  • Pipeline.

Description of pharmaceutical companies generally is limited to activities with respect to TPD for publicly known in-house activities, for R&D collaboration and licensing and for acquisitions (Merck, Bayer, Amgen and Bristol Myers Squib).

The heterogenous profiles of the 69 technology companies demands assignation to “clusters” of companies with similar characteristics to allow a systematic comparison of 33 pure-play TPD technology companies focused on proteasomal pathway or non-proteasomal pathway technologies; 26 technologically diversified companies with TPD technologies; and the remainder of 10 companies.

Specific profiles are provided for 31 TPD technologies, separately for proteasomal molecular glue/monovalent degrader; proteasomal heterobifunctional degraders, lysosomal & autophagy pathway degraders and the remainder.

Specific profiles are provided for 48 TPD drug candidates, separately for the same four TPD modalities as for TPD technologies.

All information in the three chapters of Company Profiles, Technology Profiles and Drug Candidate Profiles are fully referenced with 117 scientific references, in most cases with hyperlinks with immediate online access to the source of information (abstracts, Poster, Presentations). Non-scientific references, such as press releases, annual reports or company presentations, are disclosed within the text with an embedded hyperlink leading to the source of information. Details about R&D strategy, collaboration and licensing agreements, acquisitions, financing rounds and sources are described in the company profiles.

What will you find in the report?

  • Profiles of pure-play and diversified Targeted Protein Degrader (TPD technology companies;
  • Description of Big Pharma’s role in the field (in-house R&D, partnering, acqusition and investing);
  • Comprehensive description and analysis of emerging proteasomal and lysosomal/autophagic TPD technologies;
  • TPD Technology selection and preferences of major pharma;
  • Analysis of TPD technologies;
  • Technologies for discovery of molecular glues, difficult to drug targets and E3 ligase binders;
  • Pharmacologic profiles of Targeted Protein Degraders (TPD);
  • Target selection, pipeline analysis and competition of drug candidates;
  • Description and analysis of financing rounds (capital raised, investors);
  • Economic terms of collaboration and licensing deals;
  • Sources of financing.

Who will benefit from the report?

  • Venture capital, private equity and investment managers;
  • Managers of Big Pharma venture capital firms;
  • Financial analysts;
  • Business development and licensing (BDL) specialists;
  • CEO, COO and managing directors;
  • Corporate strategy analysts and managers;
  • Chief Technology Officer;
  • R&D Portfolio, Technology and Strategy Management;
  • Clinical and preclinical development specialists.

Table of Contents

            Abbreviations

 

1          Executive Summary

 

2          Introduction, Overview & Methodology

 

3          Analysis of TPD Stakeholders

 

3.1       Targeted Protein Degradation (TPD) Technology Companies

3.1.1    Overview

3.1.2    Pure-Play TPD Companies Focused on Molecular Glue & Monovalent Proteasomal Degraders

3.1.3    Pure-Play TPD Companies Focused on Heterobifunctional Proteasomal Degraders

3.1.4    Pure-Play TPD Companies Focused on Molecular Glue & Heterobifunctional Proteasomal Degraders

3.1.5    Pure-Play TPD Companies Focused on Lysosomal & Autophagic (Non-Proteasomal) Degradation Technologies

3.1.6    Diversified Technology Companies with One Focus on Heterobifunctional Proteasomal Degraders

3.1.7    Diversified Technology Companies with Various TPD Technology Profiles

3.1.8    Remainder of Technology Companies with Various TPD Technology Profiles

 

3.2       Pharmaceutical Companies with TPD Interests

3.2.1    Overview of Major Pharma Companies as Stakeholders in TPD

3.2.2    Profile of Major Pharma’s Interest in Targeted Protein Degradation (TPD) R&D

3.2.3    Scope of Major Pharma‘s Partnering Activities in Targeted Protein Degradation (TPD)

 

4          Analysis of TPD Technologies

 

4.1       Analysis of Molecular Glue & Monovalent Proteasomal TPD Technologies

4.2       Analysis of Heterobifunctional Proteasomal TPD Technologies

4.3       Analysis of Lysosomal & Autophagy Pathway TPD Technologies

 

5          Analysis of TPD Pipeline, Targets and Product Candidates

 

5.1       Molecular Glue & Monovalent Proteasomal Targeted Protein Degraders

5.1.1    Clinical & Non-Clinical Development Pipeline of Molecular Glue Degraders: Targets and Experience

5.1.2    Preclinical R&D Pipeline & Targets of Molecular Glue & Monovalent Protein Degraders

 

5.2       Heterobifunctional Proteasomal Targeted Protein Degraders

5.2.1    Clinical & Non-Clinical Development Pipeline of Heterobifunctional Degraders

5.2.2    Preclinical R&D Pipeline of Heterobifunctional Degraders

5.2.3    Protein-of-Interest Targets and E3 Ligases Addressed by Heterobifunctional Proteasomal Degraders

5.2.4    E3 Ligases and Binders

 

5.3       Lysosomal & Autophagy Pathway Protein Degraders

 

5.4       Remainder of Targeted Protein Degraders

 

6          Business, Financing & Partnering

 

7          Profiles of Stakeholders in Targeted Protein Degradation (TPD)

 

7.1       Pure-Play TPD Companies Focused on Molecular Glue & Monovalent Proteasomal Degraders

7.1.1    Coho Therapeutics

7.1.2    Degron Therapeutics

7.1.3    Dunad Therapeutics

7.1.4    f5 Therapeutics

7.1.5    Monte Rosa Therapeutics

7.1.6    Neomorph

7.1.7    Plexium

7.1.8    Proxygen

7.1.9    Seed Therapeutics

7.1.10  Venquis Therapeutics

 

7.2       Pure-Play TPD Companies Focused on Heterobifunctional Proteasomal Degraders

7.2.1    Amphista Therapeutics

7.2.2    Arvinas

7.2.3    Cullgen

7.2.4    Dialectic Therapeutics

7.2.5    FIMECS

7.2.6    Orum Therapeutics

7.2.7    PolyProx Therapeutics

7.2.8    Ranok Therapeutics

7.2.9    Ubix Therapeutics

 

7.3       Pure-Play TPD Companies Focused on Molecular Glue & Heterobifunctional Proteasomal Degraders

7.3.1    AnHorn Medicines

7.3.2    C4 Therapeutics

7.3.3    Captor Therapeutics

7.3.4    Celeris Therapeutics

7.3.5    Kymera Therapeutics

7.3.6    Pin Therapeutics

7.3.7    ProteoVant Therapeutics

7.3.8    Uppthera

 

7.4       Pure-Play TPD Companies Focused on Lysosomal & Autophagic (Non-Proteasomal) Degraders

7.4.1    Lycia Therapeutics

7.4.2    AUTOTAC Bio

7.4.3    Calporta Therapeutics (acquired by Merck)

7.4.4    Caraway Therapeutics

7.4.5    Casma Therapeutics

7.4.6    PAQ Therapeutics

 

7.5       Diversified Technology Companies with One Focus on Heterobifunctional Proteasomal Degraders

7.5.1    Accutar Biotechnology

7.5.2    Aurigene Discovery Technologies

7.5.3    BeiGene

7.5.4    Foghorn Therapeutics

7.5.5    Frontier Medicines

7.5.6    Haisco Pharmaceutical Group

7.5.7    Hinova Pharmaceuticals

7.5.8    Jing Medicine Technology

7.5.9    Kintor Pharmaceuticals

7.5.10  Nurix Therapeutics

7.5.11  Polymed Biopharma

7.5.12  Progenra

7.5.13  Ribon Therapeutics

7.5.14  Ryvu Therapeutics

7.5.15  VectorY

7.5.16  Voronoi (B2S Bio)

7.5.17  XPose Therapeutics

 

7.6       Diversified Technology Companies with Various TPD Technology Profiles

7.6.1    Orionis Therapeutics

7.6.2    Kangpu Biopharmaceutical Co.

7.6.3    BioTheryX

7.6.4    Biohaven

7.6.5    Vividion Therapeutics (acquired by Bayer)

7.6.6    Phoremost

7.6.7    Origami Therapeutics

7.6.8    Prazer Therapeutics

7.6.9    Prelude Therapeutics

 

7.7       Remainder of Techology Companies with Various TPD Technology Profiles

7.7.1    Ascentage Pharmaceuticals

7.7.2    Cullinan Oncology

7.7.3    Janpix – Centessa Pharmaceuticals

7.7.4    JW Pharmaceuticals

7.7.5    NeoImmuneTech

7.7.6    Salarius Pharmaceuticals

7.7.7    HB Therapeutics

7.7.8    Isoprene Pharmaceuticals

7.7.9    Ligature Therapeutics

7.7.10  Trilo Therapeutics

 

7.8       Pharmaceutical Companies with Stakes in Targeted Protein Degradation

7.8.1    AbbVie

7.8.2    Almirall

7.8.3    Amgen

7.8.4    Bayer

7.8.5    Biogen

7.8.6    Boehringer Ingelheim

7.8.7    Bristol Myers Squibb

7.8.8    Calico

7.8.9    Debiopharm

7.8.10  Eisai

7.8.11  Eli Lilly

7.8.12  Fosun Pharma

7.8.13  Gilead Sciences

7.8.14  GlaxoSmithKline

7.8.15  Janssen

7.8.16  Merck & Co

7.8.17  Merck KGaA

7.8.18  Novartis

7.8.19  Pfizer

7.8.20  Roche

7.8.21  Sanofi

7.8.22  SK Holdings

7.8.23  Vertex Pharmaceuticals

 

7.9       Academia with TPD Industry Partnerships

7.9.1    Center for Protein Degradation (CPD) at Dana-Farber Cancer Institute

7.9.2    Centre for Targeted Protein Degradation (CeTPD) at University of Dundee

7.9.3    Targeted Protein Degradation and Drug Discovery Laboratory at IRB Barcelona

 

8          Profiles of Targeted Protein Degradation (TPD) Technologies

 

8.1       Profiles of Molecular Glue & Monovalent TPD Technologies

8.1.1    Allo-Glue Platform – Orionis

8.1.2    DELPhe Technology Platform – Plexium

8.1.3    Monovalent TPD Technology – Dunad

8.1.4    NExMods Platform – f5 Therapeutics

8.1.5    Optigrade Technology Platform – Captor

8.1.6    Protein Homeostatic Modulators (PHM) – BioTheryX

8.1.7    QuEEN Platform – Monte Rosa

8.1.8    TORPEDO Platform – C4 Therapeutics

 

8.2       Profiles of Heterobifunctional Proteasomal TPD Technologies

8.2.1    ACCU-Degron Technology Platform – Accutar

8.2.2    AIMCADD Platform for Discovery of BIGPRO Protein Degraders – AnHorn

8.2.3    ALMOND Technology – Aurigene

8.2.4    Amphista Degrader Technology – Amphista

8.2.5    Antibody neoDegrader Conjugate (AnDC) Technology – Orum

8.2.6    CDAC Technology – BeiGene

8.2.7    Chaperone-Mediated Protein Degradation (CHAMP) Technology – Ranok

8.2.8    Degraducer Technology – Ubix

8.2.9    DELigase Technology Platform – Nurix

8.2.10  “Drug the Undruggable Targets” Discovery Platform – Frontier

8.2.11  Pegasus Drug Discovery Platform – Kymera

8.2.12  PROTAC Discovery Engine – Arvinas

8.2.13  RaPPIDS Technology Platform – FIMECS

8.2.14  SITESEEKER Target Discovery Platform – PhoreMost

8.2.15  uSMITE Technology – Cullgen

 

8.3       Profiles of Lysosomal & Autophagy Pathway TPD Technologies

8.3.1    ATTEC Technology – PAQ

8.3.2    Autophagy Degrader Platform (ADP) – Casma

8.3.3    AUTOTAC Technology – AUTOTAC

8.3.4    Lysosomal Drug Discovery Platform – Caraway

8.3.5    LYTAC Technology Platform – Lycia

8.3.6    Molecular Degrader of Extracellular Protein (MoDE) Platform – Biohaven

 

8.4       Other TPD-Related Technologies

8.4.1    Chemoproteomics Platform for Discovery of E3 Ligands – Vividion

8.4.2    ORICISION Technology Platform – Origami

 

9          Profiles of TPD Product Candidates

 

9.1       Molecular Glue & Monovalent Protein Degraders

9.1.1    AMG-193

9.1.2    BRD4 Monovalent Degrader

9.1.3    BTX-1188

9.1.4    CC-90009; Eragidomide

9.1.5    CC-91633; BMS-986397

9.1.6    CC-92480

9.1.7    CC-99282

9.1.8    CFT7455

9.1.9    Iberdomide (CC-220)

9.1.10  JPX-1188

9.1.11  KPG-121

9.1.12  KPG-818

9.1.13  MRT-2359

9.1.14  SP-3164

 

9.2       Heterobifunctional Proteasomal Targeted Protein Degraders

9.2.1    AC-176

9.2.2    AC0682

9.2.3    APG-265

9.2.4    ARD-1671

9.2.5    ARV-471

9.2.6    ARV-766

9.2.7    AU-19820

9.2.8    Bavdegalutamide; ARV-110

9.2.9    BCL6 PROTAC

9.2.10  BGB-16673

9.2.11  CC-94676

9.2.12  CFT1946

9.2.13  CFT8634

9.2.14  CFT8919

9.2.15  CT-03

9.2.16  DT2216

9.2.17  FHD-609

9.2.18  FIM-01

9.2.19  GT-19506

9.2.20  GT-20029

9.2.21  HP518

9.2.22  KT-253

9.2.23  KT-333

9.2.24  KT-413

9.2.25  KT-474; SAR444656

9.2.26  NX-2127

9.2.27  NX-5948

9.2.28  RBN012811

9.2.29  RNK05047

9.2.30  SD-436

9.2.31  UBX-303

 

9.3       Lysosomal & Autophagy Pathway Protein Degraders

9.3.1    TMEM175 Program

9.3.2    TRPML1 Modulators

 

9.4       Remainder of Targeted Protein Degraders – Not Defined

9.4.1    HB-007

9.4.2    Mnk1/2 Degraders

9.4.3    PRT-SCA2

 

10        References

 

ADDENDUM: Competitor Analysis        

Add 1  Molecular Glue & Monovalent Small Molecule Proteasomal Targeted Protein Degradation

Add 2  Heterobifunctional Proteasomal Targeted Protein Degradation

Add 3  Lysosomal & Autophagy Pathway Targeted Protein Degradation

Add 4  Remainder of Targeted Protein Degradation

Figures & Tables

Table 1           Assignation to Clusters of Technology Companies Active in the TPD Field

Table 2           Overview of Pure-Play, Cluster 1 Companies – Focused on Molecular Glue & Monovalent Proteasomal Degraders

Table 3           Overview of Pure-Play, Cluster 2 Companies – Focused on Heterobifunctional Proteasomal Degraders

Table 4           Overview of Pure Play, Cluster 3 Companies – Focused on Molecular Glue & Heterobifunctional Proteasomal Degraders

Table 5           Overview of Pure Play, Cluster 4 Companies – Focused on Lysosomal & Autophagy (Non-Proteasomal) Degraders

Table 6           Overview of Diversified Cluster 5 Companies – with One Focus on Heterobifunctional Proteasomal Degraders

Table 7           Overview of Diversified Cluster 6 Companies with Various TPD Technology Profiles

Table 8           Overview of Cluster 7 Companies with Various TPD Technology Profiles

Table 9           Overview of Major Pharma Stakes in TPD

Table 10         Profile of Major Pharma‘s Interests in Targeted Protein Degradation (TPD) R&D

Table 11         Scope of Major Pharma‘s Partnering Activities in Targeted Protein Degradation (TPD)

Table 12         Overview of Molecular Glue & Monovalent Proteasomal Protein Degrader Discovery Technologies

Table 13         Overview of Heterobifunctional Proteasomal Protein Degrader Discovery Technologies

Table 14         Overview of Lysosomal & Autophagic Pathway TPD Discovery Technologies

Table 15         Overview of Remainder of TPD Discovery Technologies

Table 16         Overview of Targeted Protein Degrader (TPD) Pipeline

Table 17         Pipeline of Clinical & Non-Clinical Development Stage Molecular Glue & Monovalent Protein Degraders

Table 18         Preclinical Pipeline and Targets of Molecular Glue & Monovalent Protein Degraders

Table 19         Pipeline of Clinical & Non-Clinical Development Stage Heterobifunctional Proteasomal Protein Degraders

Table 20         Preclinical Pipeline of Heterobifunctional Proteasomal Protein Degraders

Table 21         Overview of Proteins-of-Interest for Heterobifunctional Proteasomal Degraders

Table 22         Lysosomal Pathway Targeted Protein Degraders

Table 23         Autophagy Pathway Protein Degraders

Table 24         Remainder of Targeted Protein Degraders

Table 25         Sources of Financing for TPD Technology Companies

Table 26         Investors of TPD Technology Companies

Table 27         Partnering Terms of Agreements between TPD Technology Companies and Major Pharmaceutical Companies

Table 28         Molecular Glue Degrader Pipeline of Monte Rosa Therapeutics

Table 29         Discovery Pipeline of Plexium’s DELPhe-Derived Targeted Protein Degraders

Table 30         Overview of Arvinas’ Partnerships for Targeted Protein Degradation

Table 31         Arvinas’ PROTAC Degrader Pipeline

Table 32         C4 Therapeutics’ Proprietary MonoDAC & BiDAC Pipeline

Table 33         Targeted Protein Degrader Pipeline of Captor Therapeutics

Table 34         Kymera Therapeutics’ Pipeline of Targeted Protein Degraders

Table 35         Targeted Protein Degrader Pipeline of Proteoant Therapeutics

Table 36         AUTOTAC Discovery Programs of AUTOTAC Bio

Table 37         Accutar Biotechnology’s Pipeline of Small Molecule Chimeric Degraders

Table 38         Targeted Protein Degrader Pipeline of Aurigene Discovery Technologies

Table 39         Foghorn Therapeutics’ Targeted Protein Degrader Pipeline

Table 40         Nurix Therapeutics’ Pipeline of Protein Degradation Chimeric Targeting Molecules (CTMs)

Table 41         Kangpu Biopharmaceuticals’ Pipeline of Cereblon Modulators

Table 42         Discovery of SPiDEM Molecules for Targeted Protein Degradation by Prazer Therapeutics

Table 43         CELMoD R&D Pipeline of Bristol Myers Squibb

AbbVie

Accelero Biostructures

Amgen

Amphista Therapeutics

AnHorn Medicines

Arvinas

Ascentage Pharma

Aurigene Discovery

AUTOTAC Bio

Bayer

BeiGene

Biogen

Biohaven Pharmaceutical Holding Company

BioTheryX

Blueprint Medicines

Boehringer Ingelheim

Bristol Myers Squibb

C4 Therapeutics

Calico

Calporta Therapeutics

Captor Therapeutics

Caraway Therapeutics

Casma Therapeutics

Celeris Therapeutics

Centessa Pharmaceuticals

Coho Therapeutics

ComInnex

Cullgen

Cullinan Oncology

Dalriada

Deargen

Debiopharm

Degron Therapeutics

Dialectic Therapeutics

Dunad Therapeutics

Eli Lilly

f5 Therapeutics

FIMECS

Frontier Medicines

Gilead Sciences

GlaxoSmithKline

Haisco Pharmaceutical Group

Hinova Pharmaceuticals

HitGen

Hoth Therapeutics

Insilico Medicines

Isoprene Pharmaceuticals

Janpix / Centessa Pharmaceuticals

Janssen Pharmaceutical Group of Companies

JW Pharmaceutical

Kangpu Biopharmaceuticals

Kymera Therapeutics

Lycia Therapeutics

Macroceutics (Hotspot Therapeutics)

Merck & Co

Merck KGaA

Monte Rosa Therapeutics

NeoImmuneTech

Novartis

Nurix Therapeutics

Origami Therapeutics

Orionis Biosciences

Orum Therapeutics

Pfizer

Pin Therapeutics

Plexion

Polymed Biopharmaceuticals

PolyProx Therapeutics

Prazer Therapeutics

Progenra

Proteovant Therapeutics

Proxygen

Ranok Therapeutics

Ribon Therapeutics

Roche

Ryvu Therapeutics

Sanofi

Seed Therapeutics

SK Holdings

Sosei Heptares

Trilo Therapeutics

Ubix Therapeutics

University of Dundee (Centre for Targeted Protein Degradation)

Uppthera

VectorY Therapeutics

Venquis Therapeutics

Vertex Pharmaceuticals

Vipergen

Vividion Therapeutics

Voronoi

XPose Therapeutics

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